Over the past several years, this laboratory has been interested in the proposition that some of the symptoms of hepatic failure result from the accumulation of false neurochemical transmitters and deranged cerebral transmission in hepatic coma. This view differs from the classical toxic theory of hepatic coma in which certain specific toxins, i.e., ammonia or short chain fatty acids are responsible for poisoning the metabolism of the brain. Over the past several years, evidence has gradually accumulated that the derangement in central neurotransmission is secondary to a derangement in amino acid metabolism peripherally, and with deranged profile of plasma, and thus brain amino acids in hepatic encephalopathy. Improvements in hepatic encephalopathy have been related to improvements in plasma and thus brain amino acid patterns. In the ensuing year, we hope to pursue this direction and clarify the exact synthetic pathways which are deranged in the synthesis of norepinephrine, the increased synthesis of octopamine, and the increased presence of serotonin which presumably is present to increased brain tryptophan. In addition, using various diet approaches, we hope to achieve changes in brain central neurotransmitters in rats with liver disease secondary to end-to-side portacaval shunt. These findings have significant implications for etiology and therapy of hepatic coma.